The Significance of an Oncogene of MCF-7 Breast Cancer Cell Line
The MCF-7 Breast Cancer Cell Line
MCF-7 is a line derived from cells obtained in 1970 from the breast tumor of a 69-year old woman. Malignant adenocarcinoma cells were obtained from her pleural fluid and established in culture and given the name MCF-7.
MCF-7 cells are useful for in vitro studies on breast cancer because the line has retained several characteristics of mammary epithelium, including the ability to process estrogen. Genetically, the MCF-7 line has changed over time. Originally, it was described as having 85 chromosomes, but this is now reduced to 69.
MCF-7 expresses several oncogenes including c-myc and shows mutations in the tumor suppressor gene p53.
Oncogenes are genes whose activation can contribute to the development of cancer. Generally a gene is defined as an oncogenes when it is shown to be activated in human tumor cells and that experimental activation in cell culture or animal models causes malignancy. Many oncogenes have been characterized in human cancers, but few have been shown to be crucial in the progression of breast cancer.
The c-myc Oncogene of MCF-7 Cells
- The c-myc oncogene on chromosome 8q24 encodes a nuclear phosphoprotein that acts as a transcriptional regulator involved in cellular proliferation, differentiation and apoptosis (cell death).
- c-myc is amplified and overexpressed in 15%–25% of breast tumors and has been associated with poor prognosis (outcome).
- The c-myc oncogene of MCF-7 is associated with breast cancer. However it is unclear whether c-myc expression alone is sufficient for breast cancer to develop.
- c-myc appears to play a role in hormone responsiveness and chemotherapy resistance.
- Antisense to c-myc can affect cell growth rate in some breast cancer lines and animal models.
- Antisense clinical trials targeting c-myc have been carried out.
The p53 Tumor Suppressor Gene
- p53 is probably the most-studied tumor suppressor gene. Mutations of p53 are estimated to occur in up to half of all human cancers and in approximately 20%–30% of breast cancers.
- The p53 gene is located on chromosome 17p and codes for a 393-kDa protein which has multiple functions.
- Under normal conditions p53 acts as a regulating mechanism for cell division.
- Agents that damage DNA e.g. gamma irradiation, are associated with rapid increases in the levels of p53 protein within the cell.
- When activated, p53 can directly influence a number of genes, temporarily stop cell cycle and allow DNA repair to occur.
- p53 protein can also trigger apoptosis (a form of cell death) or stimulate cells to differentiate into a different type.
- Abnormalities of p53 expression have been associated with poor prognosis in breast cancer patients.
Oncogenes and tumor suppressor genes in breast cancer: potential diagnostic and therapeutic applications. C.Osborne, P.Wilson, D.Tripathy. The Oncologist, 2004, Vol 9, P361-77.
mcf7.com - Web page with information on the MCF-7 cell line and how it was derived